ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.5396C>T (p.Ala1799Val)

gnomAD frequency: 0.00001  dbSNP: rs770450108
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000206075 SCV000260254 uncertain significance Hereditary breast ovarian cancer syndrome 2023-09-14 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 220028). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. This variant is present in population databases (rs770450108, gnomAD 0.0009%). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1799 of the BRCA2 protein (p.Ala1799Val). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA2 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000222205 SCV000273122 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-16 criteria provided, single submitter clinical testing The p.A1799V variant (also known as c.5396C>T), located in coding exon 10 of the BRCA2 gene, results from a C to T substitution at nucleotide position 5396. The alanine at codon 1799 is replaced by valine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759625 SCV000889066 uncertain significance not provided 2023-05-01 criteria provided, single submitter clinical testing The variant has not been reported in individuals with BRCA2-related conditions in the published literature. The frequency of this variant in the general population, 0.000004 (1/251098 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant
Color Diagnostics, LLC DBA Color Health RCV000222205 SCV000906753 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-28 criteria provided, single submitter clinical testing This missense variant replaces alanine with valine at codon 1799 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BRCA2-related disorders in the literature. This variant has been identified in 1/251098 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
GeneDx RCV000759625 SCV001816224 uncertain significance not provided 2020-11-12 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in at least one individual with advanced cancer, type not specified (Mandelker 2017); Also known as 5624C>T; This variant is associated with the following publications: (PMID: 28873162)
University of Washington Department of Laboratory Medicine, University of Washington RCV000222205 SCV003847217 likely benign Hereditary cancer-predisposing syndrome 2023-03-23 criteria provided, single submitter curation Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
All of Us Research Program, National Institutes of Health RCV003997606 SCV004846571 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2023-11-30 criteria provided, single submitter clinical testing

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